The objective of this study is to understand the reasons for the losses of enzymes of central cholinergic neurons in human aging, and in senile dementia of the Alzheimer type (SDAT). Using a specific antiserum against purified human choline acetyltransferase (ChAT), we will determine whether reductions in the activity of this enzyme are due to changes in its quality or in its quantity. We will search for antibodies to ChAT in autopsied brain tissue and in serum from cases of ADAT and in the normal elderly. We will assay ChAT, acetylcholinesterase (AChE), and concentrations of cholinergic receptors in the central nervous system of both normal individuals and cases of SDAT coming to autopsy. The results of these studies will be correlated with detailed psychological, morphometric, and pathologic data on the same cases. We will search for age-related changes in the enzymes and receptors of the cholinergic system in rat brain. If a decrement in ChAT activity is found, we will explore the quality and quantity of the enzyme molecules present, and will investigate rates of ChAT synthesis and degradation in young and old animals. We will attempt to reproduce some of the neurochemical features of SDAT in animals by chronic treatment with a specific inhibitor of the high affinity choline uptake system.